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data/mitotic_machinery_matrix.json

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+{
+  "title": "Mitotic Spindle Assembly Checkpoint & Centrosome Interactome Matrix",
+  "description": "Biochemical and macromolecular properties of key mitotic proteins in the MVA syndrome network.",
+  "proteins": [
+    {
+      "protein": "BUBR1 (BUB1B)",
+      "uniprot": "O60566",
+      "length_aa": 1050,
+      "subcellular_location": "Kinetochore Corona / Spindle Microtubules",
+      "biochemical_function": "Serine/Threonine Protein Kinase & Pseudo-kinase; directly binds and inhibits CDC20 to block APC/C.",
+      "complex": "Mitotic Checkpoint Complex (MCC: BUBR1-BUB3-MAD2-CDC20)",
+      "mva_type": "MVA Type 1 (MIM#257300)",
+      "proband_findings": "63 variants detected; multiple heterozygous alleles spanning catalytic and CDC20-binding domains."
+    },
+    {
+      "protein": "Centrosomal Protein 57 (CEP57)",
+      "uniprot": "Q86XR8",
+      "length_aa": 500,
+      "subcellular_location": "Centrosomal Inner Core Barrel",
+      "biochemical_function": "Microtubule-bundling homodimer; anchors pericentriolar material and nucleates spindle fibers.",
+      "complex": "Centrosomal Core Scaffold",
+      "mva_type": "MVA Type 2 (MIM#614114)",
+      "proband_findings": "10 variants detected in 11q21 locus; directly correlates with proband congenital nephrocalcinosis."
+    },
+    {
+      "protein": "TRIP13 AAA+ ATPase",
+      "uniprot": "Q15645",
+      "length_aa": 432,
+      "subcellular_location": "Cytoplasm & Kinetochore Matrix",
+      "biochemical_function": "Hexameric AAA+ ATPase; mechanically unfolds MAD2 C-terminal safety-belt, converting active C-MAD2 to O-MAD2.",
+      "complex": "SAC Silencing & Inactivation Engine",
+      "mva_type": "MVA Type 3 (MIM#617598)",
+      "proband_findings": "3 variants including high-confidence mosaic somatic driver at VAF=0.286."
+    },
+    {
+      "protein": "Centrosomal Protein 192 (CEP192)",
+      "uniprot": "Q8TEP8",
+      "length_aa": 1941,
+      "subcellular_location": "Pericentriolar Material (PCM)",
+      "biochemical_function": "Essential scaffold for AURKA and PLK1 phosphorylation cascade required for centrosome maturation.",
+      "complex": "Centrosome Maturation Complex",
+      "mva_type": "MVA Type 4 (MIM#619934)",
+      "proband_findings": "219 variants across 18p11.21; highest total burden among centrosomal candidate genes."
+    },
+    {
+      "protein": "MAD1L1 (Mitotic Arrest Deficient 1)",
+      "uniprot": "Q9Y6D9",
+      "length_aa": 718,
+      "subcellular_location": "Outer Kinetochore Corona & Nuclear Pores",
+      "biochemical_function": "Coiled-coil homodimer that acts as the physical receptor for MAD2, catalyzing C-MAD2-CDC20 assembly.",
+      "complex": "MAD1-MAD2 Core Kinetochore Sensor",
+      "mva_type": "MVA Susceptibility / CIN Syndrome",
+      "proband_findings": "889 variants across 7p22.3 locus, including 51 mosaic candidate alleles."
+    },
+    {
+      "protein": "MAD2L1 (Mitotic Arrest Deficient 2)",
+      "uniprot": "Q13257",
+      "length_aa": 205,
+      "subcellular_location": "Kinetochore Corona & Cytoplasmic MCC Pool",
+      "biochemical_function": "Metastable conformational clamp (O-MAD2 vs C-MAD2) that physically captures CDC20.",
+      "complex": "Mitotic Checkpoint Complex (MCC)",
+      "mva_type": "Core SAC Component",
+      "proband_findings": "14 variants detected with high sequencing depth (>35\u00d7)."
+    },
+    {
+      "protein": "CENPE Kinesin-7",
+      "uniprot": "Q02224",
+      "length_aa": 2701,
+      "subcellular_location": "Outer Kinetochore Corona",
+      "biochemical_function": "Plus-end directed microtubule motor; powers chromosome alignment and stimulates BUBR1 kinase activity.",
+      "complex": "Kinetochore Translocation Motor",
+      "mva_type": "Microcephalic Primordial Dwarfism",
+      "proband_findings": "76 variants detected in 4q24 locus."
+    },
+    {
+      "protein": "SMC5 (Structural Maintenance 5)",
+      "uniprot": "Q8IY18",
+      "length_aa": 1101,
+      "subcellular_location": "Chromatin & Centromeric Cohesion",
+      "biochemical_function": "SMC ring ATPase; maintains chromosome architecture, resolves sister chromatid catenanes, and repairs DSBs.",
+      "complex": "SMC5/6 Chromosome Cohesion Complex",
+      "mva_type": "Atelencephaly / Microcephaly Syndrome",
+      "proband_findings": "74 variants detected in 9q21.11 locus."
+    }
+  ]
+}